Probably, the main defects underlying RTHβ correlate with TRβ2-dependent modulation of the HPT axis: When TRβ is mutated, the negative feedback, normally exerted by THs on the hypothalamus and pituitary, is impaired; as a result, the levels of TSH tend to increase and the thyroid gland is continuously stimulated, so that both its volume (goiter) and TH production increase. Here, THRB is linked to goiter.